Distinct roles of stereociliary links in the nonlinear sound processing and noise resistance of cochlear outer hair cells

Han, Wei; Shin, Jeong-Oh; Hyun, Ji Young; Min, Hyehyun; Jung, Jinsei; Lee, Jinu; Kim, Un-Kyung; Choi, Jae Young; Moon, Seok Jun; Moon, Dae Won; Bok, Jinwoong; Kim, Chul Hoon

doi:10.1073/pnas.1920229117

Cited by 17 publications

(35 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Noise-induced sensory hair cell impairment also accompanies by collapse and loss of stereocilia and destruction of their tip connection. Interestingly, the loss of tip links connecting adjacent stereocilia would increase noise susceptibility reversely [30][31][32]. Acoustic overstimulation can also cause the reduction of synaptic connections between hair cells and spiral ganglion cells, afferent fiber swelling, and auditory nerve deterioration [33][34][35][36][37].…”

Section: Cellular Pathologiesmentioning

confidence: 99%

Noise-Induced Hearing Loss: Updates on Molecular Targets and Potential Interventions

Mao

Chen

2021

Neural Plasticity

View full text Add to dashboard Cite

Noise overexposure leads to hair cell loss, synaptic ribbon reduction, and auditory nerve deterioration, resulting in transient or permanent hearing loss depending on the exposure severity. Oxidative stress, inflammation, calcium overload, glutamate excitotoxicity, and energy metabolism disturbance are the main contributors to noise-induced hearing loss (NIHL) up to now. Gene variations are also identified as NIHL related. Glucocorticoid is the only approved medication for NIHL treatment. New pharmaceuticals targeting oxidative stress, inflammation, or noise-induced neuropathy are emerging, highlighted by the nanoparticle-based drug delivery system. Given the complexity of the pathogenesis behind NIHL, deeper and more comprehensive studies still need to be fulfilled.

show abstract

Section: Cellular Pathologiesmentioning

confidence: 99%

Noise-Induced Hearing Loss: Updates on Molecular Targets and Potential Interventions

Mao

Chen

2021

Neural Plasticity

View full text Add to dashboard Cite

show abstract

“…This antibody has been custom made using the same epitope as the previously reported and well-characterized PB811 (Kazmierczak et al, 2007). -Rabbit anti-STRC primary antibody raised against amino acids 970-985 of the mouse stereocilin protein (Han et al, 2020) 0.12 nm Colloidal Gold AffiniPure Goat Anti-Rabbit IgG (EM Grade) secondary antibody (Jackson ImmunoResearch,, 1:30 dilution in blocking solution. -Gold Conjugate EM Goat F(ab')2 anti-rabbit IgG: 10 nm gold secondary antibody (BB International #14216), 1:30 dilution in blocking solution.…”

Section: Solutions For Immunogold Labelingmentioning

confidence: 99%

“…Other coating materials have also been used, including carbon (Goodyear et al, 2010). It is also possible to observe immunogold particles on samples prepared with the OTOTO technique (Heywood and Resnick, 1981;Osborne and Comis, 1991;Han et al, 2020), which is sometimes necessary in adult cochlear samples. However, while OTOTO reduces charging, osmium (atomic number 76) partially masks the gold, making the detection more challenging.…”

Section: Sputter Coatingmentioning

confidence: 99%

“…For many years, electron microscopy (EM) techniques such as transmission electron microscopy (TEM; Furness and Hackney, 1985;Kachar et al, 2000;Goodyear et al, 2005;Mogensen et al, 2007;Grillet et al, 2009;Karavitaki and Corey, 2010;Mahendrasingam et al, 2017) and scanning electron microscopy (SEM; Furness and Hackney, 1985;Kachar et al, 2000;Mogensen et al, 2007;Grillet et al, 2009;Verpy et al, 2011;Indzhykulian et al, 2013;Fang et al, 2015;Parker et al, 2016;Mahendrasingam et al, 2017;Velez-Ortega et al, 2017;Ivanchenko et al, 2020bIvanchenko et al, , 2021 have been used to study hair-cell bundles, and EM has proven to be essential for understanding stereocilia bundle development, maintenance, normal function, and dysfunction in disease. Immunogold electron microscopy techniques have been increasingly used in hearing research, providing excellent insight into structure-function relationships and protein distribution within the cell (Hasson et al, 1997;Garcia et al, 1998;Siemens et al, 2004;Furness et al, 2005;Michel et al, 2005;Goodyear et al, 2010;Verpy et al, 2011;Chen et al, 2012;Indzhykulian et al, 2013;Fang et al, 2015;Mahendrasingam et al, 2017;Wu et al, 2019;Han et al, 2020;Ivanchenko et al, 2020a).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Electron Microscopy Techniques for Investigating Structure and Composition of Hair-Cell Stereociliary Bundles

Ivanchenko

Indzhykulian

Corey

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Hair cells—the sensory cells of the vertebrate inner ear—bear at their apical surfaces a bundle of actin-filled protrusions called stereocilia, which mediate the cells’ mechanosensitivity. Hereditary deafness is often associated with morphological disorganization of stereocilia bundles, with the absence or mislocalization within stereocilia of specific proteins. Thus, stereocilia bundles are closely examined to understand most animal models of hereditary hearing loss. Because stereocilia have a diameter less than a wavelength of light, light microscopy is not adequate to reveal subtle changes in morphology or protein localization. Instead, electron microscopy (EM) has proven essential for understanding stereocilia bundle development, maintenance, normal function, and dysfunction in disease. Here we review a set of EM imaging techniques commonly used to study stereocilia, including optimal sample preparation and best imaging practices. These include conventional and immunogold transmission electron microscopy (TEM) and scanning electron microscopy (SEM), as well as focused-ion-beam scanning electron microscopy (FIB-SEM), which enables 3-D serial reconstruction of resin-embedded biological structures at a resolution of a few nanometers. Parameters for optimal sample preparation, fixation, immunogold labeling, metal coating and imaging are discussed. Special attention is given to protein localization in stereocilia using immunogold labeling. Finally, we describe the advantages and limitations of these EM techniques and their suitability for different types of studies.

show abstract

“…Hmg20a plays a role in neuronal differentiation and can preserve neuronal integrity (Lorenzo et al, 2021 ). A mutation of Tub causes loss of both tectorial membrane-attachment crowns (TM-ACs) and horizontal top connectors (HTCs), leading to severe hearing loss (Han et al, 2020 ). Sall1 mutation is responsible for Towners-Brocks syndrome (TBS) by displaying high-frequency sensorineural hearing loss in humans (Yang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

TUB and ZNF532 Promote the Atoh1-Mediated Hair Cell Regeneration in Mouse Cochleae

Rai

Zuo

2021

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Hair cell (HC) regeneration is a promising therapy for permanent sensorineural hearing loss caused by HC loss in mammals. Atoh1 has been shown to convert supporting cells (SCs) to HCs in neonatal cochleae; its combinations with other factors can improve the efficiency of HC regeneration. To identify additional transcription factors for efficient Atoh1-mediated HC regeneration, here we optimized the electroporation procedure for explant culture of neonatal mouse organs of Corti and tested multiple transcription factors, Six2, Ikzf2, Lbh, Arid3b, Hmg20 a, Tub, Sall1, and Znf532, for their potential to promote Atoh1-mediated conversion of SCs to HCs. These transcription factors are expressed highly in HCs but differentially compared to the converted HCs based on previous studies, and are also potential co-reprograming factors for Atoh1-mediated SC-to-HC conversion by literature review. P0.5 cochlear explants were electroporated with these transcription factors alone or jointly with Atoh1. We found that Sox2+ progenitors concentrated within the lateral greater epithelial ridge (GER) can be electroporated efficiently with minimal HC damage. Atoh1 ectopic expression promoted HC regeneration in Sox2+ lateral GER cells. Transcription factors Tub and Znf532, but not the other six tested, promoted the HC regeneration mediated by Atoh1, consistent with previous studies that Isl1 promotes Atoh1-mediated HC conversionex vivo and in vivo and that both Tub and Znf532 are downstream targets of Isl1. Thus, our studies revealed an optimized electroporation method that can transfect the Sox2+ lateral GER cells efficiently with minimal damage to the endogenous HCs. Our results also demonstrate the importance of the Isl1/Tub/Znf532 pathway in promoting Atoh1-mediated HC regeneration.

show abstract

Distinct roles of stereociliary links in the nonlinear sound processing and noise resistance of cochlear outer hair cells

Cited by 17 publications

References 45 publications

Noise-Induced Hearing Loss: Updates on Molecular Targets and Potential Interventions

Noise-Induced Hearing Loss: Updates on Molecular Targets and Potential Interventions

Electron Microscopy Techniques for Investigating Structure and Composition of Hair-Cell Stereociliary Bundles

TUB and ZNF532 Promote the Atoh1-Mediated Hair Cell Regeneration in Mouse Cochleae

Contact Info

Product

Resources

About